Cancer researcher awarded $946,000 to study cadmium, DNA repair
The study revolves around a specific DNA repair complex formed by the proteins PMS2 and MLH1, also known as Mutl_Alpha, which is crucial for correcting DNA errors.
By Carol McPhail
[email protected]
A researcher at the Frederick P. Whiddon College of Medicine at the University of South Alabama has been awarded a four-year $946,000 grant from the American Cancer Society to study cadmium’s effects on DNA repair.
Aishwarya Prakash, Ph.D., associate professor of biochemistry and molecular biology at the Whiddon College of Medicine and a cancer researcher at the USA Health Mitchell Cancer Institute, is leading the research, which will focus on understanding how cadmium interferes with the body’s natural defenses against cancer. Cadmium is an environmental carcinogen found in soil, cigarette smoke and foods such as shellfish and organ meats.
The study revolves around a specific DNA repair complex formed by the proteins PMS2 and MLH1, also known as Mutl_Alpha, which is crucial for correcting DNA errors – in essence, typos in our genetic code. “We aim to uncover the detailed mechanisms by which cadmium interferes with this process,” Prakash said. “Our team will use advanced biophysical and structural methods to examine changes in key enzyme regions when cadmium binds, causing loss of function.”
The researchers will investigate specific amino acids within the zinc/cadmium binding region of Mutl_Alpha. Prakash said mutations at these sites can increase the risk of cancer, particularly when there is exposure to cadmium. The findings could be especially relevant for people with Lynch syndrome, a hereditary condition that increases the lifetime risk of cancer by up to 80%. Those with Lynch syndrome are particularly vulnerable to the harmful effects of cadmium because they have only one functional copy of the DNA-correcting complex Mutl_Alpha, she said.
In addition, the team will explore the broader interactions between DNA repair errors and environmental factors that lead to cancer development. They plan to use sophisticated spatial technology to analyze endometrial tumor samples to study how changes in gene expression initiate and drive cancer.
“Our equipped lab, together with strategic collaborations, positions us to achieve significant insights into the relationship between cadmium exposure and cancer susceptibility,” Prakash said. “If successful, our research can inform environmental lifestyle choices where toxicants like cadmium might be present, such as smoking and diet.”
Collaborators on the project are John Wise, Ph.D., and Jamie Wise, Ph.D., of the University of Louisville; Andrej Wierzbicki, Ph.D., Alan Salter, Ph.D., Kevin Lee, Ph.D., and Justin Roberts, Ph.D., of the University of South Alabama; and Jennifer Scalici, M.D., of Emory University’s Winship Cancer Institute in Atlanta.
